Granulocyte colony-stimulating factor enhances protection by anti-K1 capsular IgM antibody in murine Escherichia coli sepsis.
Combined prophylactic treatment with recombinant murine granulocyte colony-stimulating factor (G-CSF) and a suboptimal dose of anti-K1 capsular IgM monoclonal antibody (MAb) significantly enhanced survival in an experimental mouse Escherichia coli O7:K1 peritonitis model compared with untreated animals (67% vs. 11% survival; P < 0.001) and with either treatment alone (67 vs. 29% and 27% survival, respectively; P < 0.01), which suggests synergism between these agents. Enhanced survival by combined treatment was associated with increased neutrophil counts in blood and peritoneal lavage fluid, lower systemic and higher levels of local tumour necrosis factor (TNF) and lower bacterial counts in blood cultures. Mouse neutrophils treated with G-CSF but not infected with E. coli showed enhanced phagocytic and respiratory burst capacity, down-regulation of L-selectin receptors and enhanced expression of Fc RII-III receptors but not of complement receptors.
Hustinx
W
W
Eijkman-Winkler Laboratory for Medical Microbiology, Utrecht University Hospital, The Netherlands.
Benaissa-Trouw
B
B
Van Kessel
K
K
Kuenen
J
J
Tavares
L
L
Kraaijeveld
K
K
Verhoef
J
J
Hoepelman
A
A
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000276:immunology; D016470:Bacteremia / Q000097:blood / Q000276:immunology / Q000628:therapy; D016667:Bacterial Capsules; D004927:Escherichia coli Infections / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D019085:Fluorescent Antibody Technique, Direct; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000627:therapeutic use*; D007075:Immunoglobulin M / Q000627:therapeutic use*; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010538:Peritonitis / Q000276:immunology / Q000401:mortality / Q000628:therapy; D010587:Phagocytosis / Q000187:drug effects; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D017452:Receptors, IgG / Q000096:biosynthesis; D018805:Sepsis / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D013534:Survival; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; C036962:capsular polysaccharide K1; D016179:Granulocyte Colony-Stimulating Factor; D016650:Fluorescein-5-isothiocyanate